A healthy woman at 28 weeks of gestation has total serum T4 measured at 16 micrograms/dL (nonpregnant reference range 5 to 12), but free T4 and TSH are within normal limits and she is clinically euthyroid. The finding of elevated total T4 is explained by:

• A Increased thyroidal secretion driven by placental TSH receptors
• B Decreased hepatic clearance of free T4
• C Reduced peripheral conversion of T4 to T3
• D Estrogen-induced increase in thyroxine-binding globulin concentration ✓

Explanation

Estrogen increases hepatic synthesis of thyroxine-binding globulin and also sialylates it, prolonging its half-life. The expanded pool of binding protein raises total hormone concentration while free T4, the biologically active fraction, remains normal, and feedback keeps TSH unchanged. Only about 0.03 percent of circulating T4 is free; measuring free hormone avoids this pitfall. Reduced conversion of T4 to T3 would lower, not raise, measurable hormone effects.

Reference: Williams Textbook of Endocrinology, 14th ed.

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